Only a quarter of women with dense breasts had higher risk for interval breast cancer

Action Points

Breast density on mammography plus breast cancer risk based on a validated breast cancer risk score can identify women most at need for supplemental imaging following screening mammography.

Women with risk ≥1.67% and extremely dense breasts and women with risk ≥2.50% and heterogeneously dense breasts are at greatest risk of developing breast cancer including advanced-stage disease.

Half of women ages 40 to 74 with dense or heterogeneously dense breasts were at low or average risk for breast cancer, and about one-quarter of those with dense breasts exhibited high rates of interval breast cancer, according to a large population-based study.

Interval cancer rates for these women were 0.58 to 0.63 and 0.72 to 0.89 per 1,000 examinations, respectively, they wrote in the Annals of Internal Medicine.

Overall, 24% of women with dense breasts had "high" interval cancer rates -- defined as greater than one case per 1,000 patients. High interval cancer rates were also observed in 47.5% of women with extremely dense breasts and a 5-year risk of developing breast cancer of 1.67% or greater, and 19.5% of women with heterogeneously dense breasts and a 5-year risk of 2.50% or greater.

Examining advanced-stage disease, high interval cancer rates were seen among women with dense or heterogeneously dense breasts who had a 5-year breast cancer risk of 2.50% or greater (>0.4 case per 1,000 examinations). Overall, this group was comprised of 21% of women ages 40 to 74 with dense breasts. When factoring in age and density, women ages 60 to 74 years with extremely dense breasts experienced an elevated rate of advanced-stage interval cancer.

In a separate interview with MedPage Today, Kerlikowske cited the "breast density law" in the state of California as a reason for her research. "For 2 years now, women have been notified that they have dense breasts, and we discuss with them that it might make them at increased risk of breast cancer," she said. "I was trying to figure out is there a way to narrow that group down to really identify people who are most at risk to having a missed cancer."

In a separate editorial, Nancy C. Dolan, MD and Mita Sanghavi Goel, MD, MPH, of Northwestern University Feinberg School of Medicine in Chicago, address the numerous problems that could potentially arise from these breast density laws.

In addition to the impact on the more than 27.6 million women who have dense breasts, they cite the dramatic increase in cost compared with the smaller increase in benefits: over $2 million per 1,000 women screened yielding 1,219 biopsies and averting 0.43 cancer deaths per year. They also comment on the lack of research on long-term outcomes due to a lack of randomized, controlled trials on the subject, and conclude resources may be better spent elsewhere.

"Resources targeted for breast density legislation would be better devoted toward more accurate identification of women at high risk for interval breast cancer, research on optimal use of imaging methods, reduction of disparities in screening and early detection, and training of front-line primary care providers on breast cancer risk assessment," Dolan and Goel wrote.

To better target supplemental imaging to the women who need it, Kerlikowske and colleagues suggest six distinct strategies to identify women who may benefit the most from supplemental imaging, based on a combination of factors including density, age, and risk:

Kerlikowske highlighted strategy 4 because it comprises the women at the greatest risk of developing interval cancer, as well as advanced-stage disease. "Among that group is all the women at risk of advanced cancer, so you're really sort of targeting the people you hope would benefit from supplemental imaging," she added.

Researchers cited a false positive rate of less than 120 per 1,000 examinations for all age and density groups except for women 40 to 49 with scattered fibroglandular densities or heterogeneously dense breasts, as well as women with low to average risk scores and heterogeneously dense breasts.

From 2002 to 2011, the study prospectively collected data from women ages 40 to 74 (n=365,426) who received 831,455 digital screening mammography exams at the BCSC imaging facilities. Breast density was measured using the Breast Imaging Reporting and Data System (BI-RADS) categories. Of these women, 2,696 were diagnosed with invasive breast cancer within 12 months of screening. Those diagnosed were more likely to be older and white, with heterogeneously or extremely dense breasts, a BCSC risk score of ≥1.67%, and a family history of breast cancer.

Limitations include that the authors did not assess the benefits of supplemental imaging, nor do they know if the standards they used for the study are related to any long-term outcomes such as breast cancer or death.

The authors concluded that breast density, along with age and breast cancer risk, should be considered "to optimize the identification of women with high interval cancer rates or high rates of false-positive results who may benefit from supplemental screening tests or alternative screening strategies."

Kerlikowske said the next steps would be to see how women at increased risk for breast cancer might respond to different types of supplemental imaging tests, such as screening ultrasound or MRI.

"Now that we know who they are, we have to figure out what will help them," she said.

Kerlikowske and colleagues were supported by the National Cancer Institute-funded Breast Cancer Surveillance Consortium.

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